There is a significant need for suitable scaffold materials in reconstructive surgery of the head and neck region. Congenital and acquired deformations of structures such as larynx, soft and hard palate, nasal, auricular, and facial bones are common, and biomaterials available for surgical repair of these objects are limited. Contracture, infection, and poor integration into the surrounding tissues are frequent problems with such materials. Clearly a tissue graft material is desired which is non-immunogenic, is not subject to gross shrinkage after implantation, and promotes the growth of endogenous vocal cord, larynx, soft and hard palate, nasal, and auricular tissues.
The naturally-occurring extracellular matrix (ECM) of the small intestinal submucosa, as well as other vertebrate sources of submucosa, has been shown to serve as a resorbable scaffold for numerous body systems. Surprisingly, it too has been found that basement membranes (stroma) prepared from liver tissue of warm-blooded vertebrates (by removing cellular components of the liver tissue) exhibit mechanical and biotropic properties suitable for use as a tissue graft material. The present invention is directed to the use of vertebrate submucosa matrices and basement membranes as tissue grafts for replacing damaged or diseased portions of head and neck soft tissue and promoting the remodeling and regeneration of the tissue graft with endogenous tissues. The submucosa matrices used in accordance with the present invention comprises highly conserved collagens, glycoproteins, proteoglycans, and glycosaminoglycans in their natural configuration and natural concentration. Vertebrate submucosa is a relatively acellular collagen-based matrix that can be isolated from animal tissues, including particularly intestinal tissue harvested from animals raised for meat production. The isolated submucosa can be used to prepare a resorbable tissue graft construct for inducing the repair of endogenous tissues.
The basement membrane graft compositions of the present invention comprise the basement membrane of organ tissue of a warm-blooded vertebrate, for example, liver tissue, substantially free, preferably devoid, of all cells (e.g., hepatocytes and bile ductal cells) of said warm-blooded vertebrate. The liver basement membrane can be implanted, or fluidized and injected, into a vertebrate host to contact damaged or defective vocal cord, larynx, soft and hard palate nasal and auricular tissues and induce the repair or replacement of said tissues in vivo.
It is known that compositions comprising the tunica submucosa and the basilar portions of the tunica mucosa of the intestine of warm-blooded vertebrates can be used as tissue graft materials in sheet form. See U.S. Pat. No. 4,902,508. The compositions described and claimed in that patent are characterized by excellent mechanical properties, including high compliance, a high burst pressure point, and an effective porosity index which allows such compositions to be used beneficially for vascular graft constructs. The graft materials disclosed in that patent are also useful in tendon, ligament and other connective tissue replacement applications. Furthermore, intestinal submucosa has been used as a scaffold for regenerating other tissues including urinary bladder and dura mater. When used in such applications the preferred graft constructs appear to serve as a matrix for the regrowth of the tissues replaced by the graft constructs. Vertebrate submucosa is a plentiful by-product of commercial meat production operations and is thus a low cost tissue graft material, especially when the submucosa is used in its native sheet configuration. Intestinal submucosa has undergone extensive immunologic testing in over 600 cross-species implants and has never been shown to elucidate a rejection reaction.
Furthermore, it is known that intestinal submucosa can be fluidized by comminution and/or protease digestion, without loss of its apparent biotropic properties, for use in less invasive methods of administration (e.g., injection or topical) to host tissues in need of repair. See U.S. Pat. No. 5,275,826 the disclosure of which is expressly incorporated herein. Fluidized comminuted intestinal tissue comprising tunica submucosa has previously been successfully used to repair and functionally augment damaged tissues including, for example, urinary bladder sphincter. Common events to tissue remodeling include widespread and rapid neovascularization, proliferation of granulation mesenchymal cells, biodegradation of implanted submucosa, and lack of immune rejection.
The present invention is directed to the use of vertebrate-derived submucosa or basement membrane matrices as a graft for the regeneration and repair of head and neck soft tissues including the larynx, vocal cords, soft and hard palate, attached gingiva, nasal and auricular tissues. Such vertebrate extracellular matrices are inexpensive, nonimmunogenic materials that induce host tissue proliferation, remodeling and regeneration upon implantation. In accordance with one embodiment of the present invention tissue graft constructs comprising submucosa or basement membrane of a warm-blooded vertebrate have been found to promote the growth of endogenous vocal cord tissues including the oral mucosal epithelium, connective tissue and skeletal muscle. The graft constructs of the present invention can be used to repair or reconstruct structures damaged by cancer or resulting from congenital defects. The method comprises replacing the damaged or diseased tissues with the construct which acts as a scaffold for endogenous cell growth and replacement of the graft construct. The scaffold is typically entirely replaced by endogenous tissues in about three to six weeks.